Summary
Isolated rat hearts with the right sympathetic nerves attached were perfused at a constant flow rate of 7 ml/min with Tyrode's solution. (-)-3H-Noradrenaline (final concentration 10–13.9 nM) was infused for 10 min to label the noradrenaline stores. After wash-out the sympathetic nerves were stimulated electrically (3 Hz, 180 impulses, 1 ms, 20–30 mA) three times (S1–S3) at intervals of 15 min. 3H-Noradrenaline and its metabolites were determined by liquid scintillation counting according to Graefe et al. (1973).
Both, nicotine 50 μM and p-aminophenethyltrimethylammonium (PAPETA) 30 μM, enhanced the 3H-noradrenaline overflow in the absence of nerve stimulation. The effect of PAPETA was biphasic and was still observed in the presence of N-methylatropine 0.1 μM. Hexamethonium 10 μM abolished the first phase only, but cocaine 10 μM antagonized both phases.
The decline of the stimulation-evoked overflow of 3H-noradrenaline from the first to the third stimulation period was similar in the absence and in the presence of cocaine 10 μM starting before S1 and perfused throughout. Cocaine 10 μM added before S2, however, enhanced the evoked overflow by 77%.
PAPETA 30 μM increased the stimulation-evoked overflow by 67% in the absence, and by 73% of the respective control in the presence, of hexamethonium 10 μM. PAPETA 30 μM failed to enhance the evoked overflow in the presence of cocaine. Hexamethonium (added before S2) did not modify the effectiveness of nerve stimulation.
Nicotine, neither when perfused from 6 min before S2, nor when added to the perfusion fluid simultaneously with the onset of nerve stimulation, caused changes in the 3H-noradrenaline output upon S2.
Upon stimulation a rather discrete increase in 3H-DOPEG overflow was observed. This increase was abolished by cocaine and/or PAPETA.
It is concluded that nicotine and PAPETA stimulate the output of 3H-noradrenaline from the rat heart sympathetic nerves by activation of nicotine receptors. However, the amount of transmitter released is small. Neither drug appeared to modulate the output of 3H-noradrenaline upon electrical nerve stimulation via nicotine receptors.
PAPETA, like cocaine, appears to block the reuptake of released transmittsrs thereby enhancing the 3H-noradrenaline overflow and reducing the overflow of 3H-DOPEG (formed intraneuronally from recaptured noradrenaline after nerve stimulation).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- DOMA:
-
3,4-dihydroxymandelic acid
- DOPEG:
-
3,4-dihydroxyphenylglycol
- MOPEG:
-
3-methoxy-4-hydroxy-phenylglycol
- NA:
-
noradrenaline
- NMN:
-
normetanephrine
- OMDA:
-
O-methylated deaminated metabolites (sum of MOPEG and VMA)
- PAPETA:
-
p-aminophenethyltrimethylammonium
- VMA:
-
3-methoxy-4-hydroxymandelic acid
References
Barlow RB, Franks F (1971) Specificity of some ganglion stimulants. Br J Pharmacol 42:137–142
Barlow RB, Thompson GM, Scott NC (1969) The affinity and activity of compounds related to nicotine on the rectus abdominis muscle of the frog (Rana pipiens). Br J Pharmacol 37:555–584
Dunnett CW (1955) A multiple comparison procedure for comparing several treatments with a control. J Am Statist Assoc 50:1096–1121
Edvinsson L, Falck B, Owman Ch (1977) Possibilities for cholinergic nerve action on smooth musculature and sympathetic axons in brain vessels mediated by muscarinic and nicotinic receptors. J Pharmacol Exp Ther 200:117–126
Engel U, Löffelholz K (1976) Presence of muscarinic inhibitory and absence of nicotinic excitatory receptors at the terminal sympathetic nerves of chicken heart. Naunyn-Schmiedeberg's Arch Pharmacol 295:225–230
Euler US, von (1972) Synthesis, uptake and storage of catecholamines in adrenergic nerves, the effect of drugs. In: Blaschko H, Muscholl E (eds) Handbook of experimental pharmacology, vol 33. Catecholamines. Springer, Berlin Heidelberg New York, pp 211–212
Fuder H, Rink D, Alt B (1981) Pirenzepine (Pi) and functional pre-and postsynaptic muscarine receptors in rat and rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 316:R52
Fuder H, Rink D, Muscholl E (1982) Sympathetic nerve stimulation on the perfused rat heart: Affinities of N-methylatropine and pirenzepine at pre-and postsynaptic muscarine receptors. Naunyn-Schmiedeberg's Arch Pharmacol (in press)
Graefe KH, Stefano FJE, Langer SZ (1973) Preferential metabolism of (-)-[3H]norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160
Holbach JH, Lindmar R, Löffelholz K (1977) DMPP and the adrenergic nerve terminal: mechanisms of noradrenaline release from vesicular and extravesicular compartments. Naunyn-Schmiedeberg's Arch Pharmacol 300:131–138
Huković S, Muscholl E (1962) Die Noradrenalin-Abgabe aus dem isolierten Kaninchenherzen bei sympathischer Nervenreizung und ihre pharmakologische Beeinflussung. Naunyn-Schmiedeberg Arch Exp Path Pharmak 244:81–96
Lindmar R (1962) Die Wirkung von 1,1-Dimethyl-4-Phenyl-Piperazinium-Jodid am isolierten Vorhof im Vergleich zur Tyraminund Nicotinwirkung. Naunyn-Schmiedebergs Arch Exp Path Pharmak 242:458–466
Lindmar R, Muscholl E (1961) Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracain uund Psicain auf die Noradrenalin-Freisetzung aus dem Herzen. Naunyn-Schmiedebergs Arch Exp Path Pharmak 242:214–227
Löffelholz K (1970a) Autoinhibition of nicotinic release of noradrenaline from postganglionic sympathetic nerves. Naunyn-Schmiedebergs Arch Pharmak 267:49–63
Löffelholz K (1970b) Nicotinic drugs and postganglionic sympathetic transmission. Naunyn-Schmiedebergs Arch Pharmakol 267:64–73
Löffelholz K (1979) Release induced by nicotinic agonists. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon Press, Oxford, pp 275–301
Muscholl E (1970) Cholinomimetic drugs and release of the adrenergic transmitter. In: Schümann HJ, Kroneberg G (eds) New aspects of storage and release mechanisms of catecholamines. Springer, Berlin Heidelberg New York, pp 181–183
Muscholl E (1980) Peripheral muscarinic control of norepinephrine release in the cardiovascular system. Am J Physiol 239:H713-H720
Roffler Tarlov S, Langer SZ (1971) The fate of 3H-norepinephrine released from isolated atria and vas deferens: effect of field stimulation. J Pharmacol Exp Ther 179:186–197
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124
Starke K, Weitzell R (1978) Is histamine involved in the sympathomimetic effect of nicotine? Naunyn-Schmiedeberg's Arch Pharmacol 304:237–248
Starke K, Steppeler A, Zumstein A, Henseling M, Trendelenburg U (1980) False labelling of commercially available 3H-catecholamines? Naunyn-Schmiedeberg's Arch Pharmacol 311:109–112
Story DF, Allen GS, Glover AB, Hope W, McCulloch MW, Rand MJ, Sarantos C (1975) Modulation of adrenergic transmission by acetylcholine. Clin Exp Pharmacol Physiol (Suppl) 2:27–33
Westfall TC, Brasted M (1972) The mechanism of action of nicotine on adrenergic neurons in the perfused guinea-pig heart. J Pharmacol Exp Ther 182:409–418
Westfall TC, Saunders J (1977) Absence of nicotinic receptors mediating the release of norepinephrine from adrenergic neurons in the rat heart. Proc Soc Exp Biol Med 156:476–479
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fuder, H., Siebenborn, R. & Muscholl, E. Nicotine receptors do not modulate the 3H-Noradrenaline release from the isolated rat heart evoked by sympathetic nerve stimulation. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 301–307 (1982). https://doi.org/10.1007/BF00501169
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00501169